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In 1795, Dr. Victor Frankenstein (Aden Young) creates a monster (Aaron Eckhart), a soulless creature patched together from corpses, and then rejects it, disgusted with what he has made. In a fit of rage, the creature kills Victor's wife Elizabeth (Virginie Le Brun) and Victor chases it to the Arctic to get revenge, but succumbs to the weather. The creature buries his creator in the Frankenstein family crypt and is then attacked by demons before being rescued by the gargoyles Ophir (Mahesh Jadu) and Keziah (Caitlin Stasey), who bring it before the gargoyle queen Leonore (Miranda Otto) and their commander Gideon (Jai Courtney). Leonore explains that they were created by the ArchangelMichael to battle demons on Earth and protect humanity. They name the creature "Adam" and invite him to join them, but he declines and departs after being given heavy, baton-like weapons to protect him, as more demons will come after him. The weapons allow him to "descend" demons (destroying their bodies and trapping their souls in Hell) as they have the symbol of the Gargoyle Order carved on them.

Throughout the centuries, Adam fends off the demons that pursue him. During a modern-day confrontation at a nightclub, a human police officer is killed. While Adam is summoned by the gargoyles once more, the demon Helek (Steve Mouzakis) reports that Adam is alive to his leader, the demon-prince Naberius (Bill Nighy), who is disguised as billionaire businessman Charles Wessex, and his right-hand man, Dekar (Kevin Grevioux). Wessex has employed scientists Terra Wade (Yvonne Strahovski) and Carl Avery (Nicholas Bell) to conduct experiments with reanimated corpses, and sends a group of demons led by his most formidable warrior, Zuriel (Socratis Otto), to attack the gargoyles' cathedral and capture Adam so he can unlock the secret to giving life.

Before Leonore can punish Adam for the police officer's death, the cathedral is attacked and Adam convinces Ophir to release him. In the ensuing battle, a number of gargoyles, including Ophir and Keziah, are "ascended" (returned to and trapped in Heaven) while Leonore is captured and brought to an abandoned theater. Gideon is instructed to bring Adam as a trade for Leonore; Adam interrogates a demon and gains the same information. Adam having escaped, Gideon descends into the vaults and takes Victor Frankenstein's journal, which was taken off of Adam's body the night they found him. He exchanges the journal for Leonore, as it contains the secrets of the experiment. Once Gideon departs with Lenore, Adam attempts to recover the journal, but is prevented from doing so as several demons attack. Descending them, Adam then follows Zuriel to the Wessex Institute, where he learns that Naberius plans to recreate Frankenstein's experiment and use thousands of reanimated corpses as hosts for souls of the descended demons. The demons will be able to return from Hell if they have soulless bodies to possess. Adam retrieves the journal and escapes and later confronts Terra before they are attacked by Zuriel. Adam manages to "descend" Zuriel.

Adam warns the remaining gargoyles of Naberius' plan, agreeing to give them the journal if they get him and Terra to safety. Leonore agrees, but sends Gideon to kill him and retrieve the journal. After a violent fight, Adam is forced to "ascend" Gideon and then decides to burn Frankenstein's journal and destroy its secrets before the gargoyles come after him. Adam evades them, leading them to the Wessex Institute where they join battle with Naberius' demons, descending Dekar early in the fight. While the battle progresses, Adam ventures into the Institute to rescue Terra, who had been kidnapped by Naberius to put the next stage of his plan into process after he killed Avery. Naberius takes his true demonic form and activates the machine. Naberius overpowers Adam and tries to have one of the demon spirits possess him, but Adam proves immune as he has grown his own soul. As the gargoyles attempt to stop the reanimated bodies, Adam carves the symbol of the Gargoyle Order on Naberius, sanctifying his very body and utterly destroying it, descending Naberius alongside all the other demons in his army, and causing the entire building to collapse.

Recognizing Adam's bravery, Leonore rescues him and Terra and forgives Adam for Gideon's death. Adam retrieves his weapons. After bidding farewell to Terra, Adam departs to begin an immortal quest to protect the humans of the world and hunt demons for selfless reasons, the attitude that had earned him his soul in the first place. In so doing, he embraces his role and his true name of "Frankenstein".

It was announced on October 7, 2011 that Aaron Eckhart would play the lead role.[11] Eckhart described his character thus: "Frankenstein is an intelligent, evolved man, and that’s how he is portrayed in this movie, for sure."[12] In November 2011, Yvonne Strahovski was cast as the female lead, a scientist working to reanimate the dead, while Miranda Otto was cast as the queen of the gargoyles.[13]Bill Nighy plays the film's villain, whom he described as a "Nasty piece of work; one of the angels descended with Satan."[14] Eckhart and Otto trained for three months with martial arts experts Ron Balicki and Diana Lee Inosanto in the Filipino martial art of Kali for their fight scenes.

The North American release was originally set for February 22, 2013,[17] and moved from its original release date of February 22, 2013 to September 13, 2013.[18] In February 2013, it was announced the film would be released in 3D.[19] In April 2013 the release date was later moved from September 13, 2013, to January 24, 2014.[20] The film saw its world premiere in Buenos Aires on January 20, 2014, after which it was released in 23 countries between January 22 and January 24. It was released in a further nine countries between January 29 and January 31.[21] On September 17, 2013, it was announced that the film would be digitally re-mastered and released in the IMAX format.[22]

On Rotten Tomatoes, it has a 3% approval rating and an average score of 3.1/10. Based on 87 reviews, the general consensus is: "Loud, incoherent, and dramatically listless, I, Frankenstein is a remarkably dull fantasy adventure that fails to generate much excitement or interest in its characters."[24] On Metacritic, the film holds a 30 (out of 100) based on 20 critics, indicating "generally unfavorable reviews".[25] In CinemaScore poll, cinema audiences gave the film an average grade of "B" from an A+ to F scale.[26]

Mike McCahill of The Guardian gave the film 2 stars and Total Film also gave it 2 stars. Among the film's three positive reviews on Rotten Tomatoes was Ben Sachs, who said of the film "The novel premise quickly gives way to lots of chaotic action, though there are numerous incidental pleasures throughout."

In the United States and Canada, the film was released in a total of 2,763 theaters of which 3D and IMAX comprised 95% of the total theaters. It earned $8.6 million in its opening weekend, which was below expectations. About 65% of the grosses came from 3D showings.[26] Despite its disappointing opening in North America, it however had a successful opening in Russia with $6.3 million from 1,846 screens.[27] At the end of its theatrical run, the film grossed a total of $19 million in North America and $52 million elsewhere, for a worldwide total of $71.1 million surpassing its $65 million budget.[3]

Much doubt has been cast over a sequel due to the film's lackluster box office performance, though Kevin Grevioux, creator of the graphic novel and the Underworld film series, had earlier expressed interest in making more I, Frankenstein films along with an Underworld crossover film. He stated in a pre-release interview that, in an early draft of his screenplay, Kate Beckinsale would have made a post-credits cameo appearance as Selene and that there would have been UnderworldEaster eggs, but none of this was used.[28] Subsequent releases in the series such as the fifth film titled Underworld: Blood Wars, which was released internationally on November 24, 2016, and in the United States on January 6, 2017, showed no cross-over of themes.